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Growth factors and sepsis

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https://www.readbyqxmd.com/read/29157085/sequential-occurrence-of-small-cell-and-non-small-lung-cancer-in-a-male-patient-is-it-a-transformation
#1
Ahsan Wahab, Kavitha Kesari, Siddique Chaudhary, Mahin Khan, Hafiz Khan, Susan Smith, Yanis Boumber
Lung cancer is one of the leading causes of cancer-related mortality and is categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). We present a patient with epidermal growth factor receptor (EGFR)-mutant-NSCLC who developed metastatic SCLC after initial therapy with second-generation EGFR-tyrosine kinase inhibitor, afatinib. A 65-year-old male non-smoker was diagnosed with adenocarcinoma of the right lung, stage IVA (M1a). Due to tumor positivity for EGFR-Exon 19 deletion, the patient was started on oral afatinib, which resulted in a partial response...
November 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29122754/limited-role-of-kininogen-in-the-host-response-during-gram-negative-pneumonia-derived-sepsis
#2
Chao Ding, Cornelis Van't Veer, Joris J T H Roelofs, Meenal Shukla, Keith R McCrae, Alexey S Revenko, Jeff Crosby, Tom van der Poll
High molecular weight kininogen (HK), together with Factor XI, Factor XII and prekallikrein, is part of the contact system, which has proinflammatory, prothrombotic and vasoactive properties. We hypothesized that HK plays a role in the host response during pneumonia derived sepsis. To this end mice were depleted of kininogen (KNG) to plasma HK levels of 28% of normal by repeated treatment with a specific antisense oligonucleotide (KNG ASO) for three weeks prior to infection with the common human sepsis pathogen Klebsiella pneumoniae via the airways...
November 9, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29118755/apoptotic-cells-induced-signaling-for-immune-homeostasis-in-macrophages-and-dendritic-cells
#3
REVIEW
Uriel Trahtemberg, Dror Mevorach
Inefficient and abnormal clearance of apoptotic cells (efferocytosis) contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs), and contributes to maintenance of peripheral tolerance. As many as 3 × 10(8) cells undergo apoptosis every hour in our bodies, and one of the primary "eat me" signals expressed by apoptotic cells is phosphatidylserine (PtdSer)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29074341/the-clinical-significance-of-endocardial-endothelial-dysfunction
#4
REVIEW
Sonja Smiljic
Endocardial endothelium (EE) is essential in the embryonic development of the heart, the optimal contractility and rhythm as well as the remodeling of the heart. Endocardial endothelium affect the contractility of cardiomyocytes through paracrine signaling substances such as nitric oxide (NO), endothelin (ET-1), prostaglandins (PGI2, PGF2, PGE2) and angiotensin II (ANG II). Typical lesions of endocardial endothelium have been described in atrial fibrillation, ischemia/reperfusion injury, cardiac hypertrophy, heart failure, sepsis, myocardial infarction, inflammation and thrombosis...
September 21, 2017: Medicina
https://www.readbyqxmd.com/read/29046432/alk-is-a-therapeutic-target-for-lethal-sepsis
#5
Ling Zeng, Rui Kang, Shan Zhu, Xiao Wang, Lizhi Cao, Haichao Wang, Timothy R Billiar, Jianxin Jiang, Daolin Tang
Sepsis, a life-threatening organ dysfunction caused by infection, is a major public health concern with limited therapeutic options. We provide evidence to support a role for anaplastic lymphoma kinase (ALK), a tumor-associated receptor tyrosine kinase, in the regulation of innate immunity during lethal sepsis. The genetic disruption of ALK expression diminishes the stimulator of interferon genes (STING)-mediated host immune response to cyclic dinucleotides in monocytes and macrophages. Mechanistically, ALK directly interacts with epidermal growth factor receptor (EGFR) to trigger serine-threonine protein kinase AKT phosphorylation and activate interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB) signaling pathways, enabling STING-dependent rigorous inflammatory responses...
October 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29042256/antiseptic-effects-of-dabrafenib-on-tgfbip-induced-septic-responses
#6
In-Chul Lee, Jong-Sup Bae
Transforming growth factor-β-induced protein (TGFBIp), an extracellular protein, is expressed on several cell types in response to TGF-β stimulation. Human umbilical vein endothelial cell (HUVEC)-derived TGFBIp functions as a mediator of sepsis. Screening of bioactive compound libraries is an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases (drug repositioning). Dabrafenib (DAB), a B-Raf inhibitor, was initially used for treating metastatic melanoma...
October 14, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29028771/mechanisms-of-thrombocytopenia-during-septic-shock-a-multiplex-cluster-analysis-of-endogenous-sepsis-mediators
#7
Alexandre Bedet, Keyvan Razazi, Florence Boissier, Mathieu Surenaud, Sophie Hue, Stéphane Giraudier, Christian Brun-Buisson, Armand Mekontso Dessap
BACKGROUND: Thrombocytopenia is a common feature of sepsis and may involve various mechanisms often related to the inflammatory response. This study aimed at evaluating factors associated with thrombocytopenia during human septic shock. In particular, we used a multiplex analysis to assess the role of endogenous sepsis mediators. METHODS: Prospective, observational study. Thrombocytopenia was defined as an absolute platelet count <100 G/L or a 50% relative decrease in platelet count during the first week of septic shock...
October 12, 2017: Shock
https://www.readbyqxmd.com/read/28983473/extracellular-signals-of-a-human-epithelial-colorectal-adenocarcinoma-caco-2-cell-line-facilitate-the-penetration-of-pseudomonas-aeruginosa-pao1-strain-through-the-mucin-layer
#8
Naoki Hayashi, Atsushi Yokotani, Masami Yamamoto, Mariko Kososhi, Mayu Morita, Chiaki Fukunishi, Nagisa Nishizawa, Naomasa Gotoh
Pseudomonas aeruginosa can penetrate the layer of mucus formed by host intestinal epithelial cells, often resulting in sepsis in immunocompromised patients. We have previously demonstrated that P. aeruginosa can penetrate the mucin layer by flagellar motility and the degradation of the mucin layer. However, it remains unclear how P. aeruginosa initially recognizes epithelial cells. Using the human epithelial colorectal adenocarcinoma (Caco-2) cell line, we investigated extracellular signaling that could facilitate the penetration of P...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28926879/-systematic-evaluation-on-effectiveness-and-safety-of-recombinant-human-growth-hormone-in-treating-adult-patients-with-severe-burn
#9
F Y Tian, B Wu, T Xu, X H Jiang
Objective: To systcmatically evaluate the effectiveness and safety of recombinant human growth hormone (rhGH) in treating adults with severe burn. Methods: Databases including PubMed, Cochrane Library, and Embase were searched using key words " burns, thermal, human growth hormone, growth hormone, hGH, and somatropin (human)" , and China Biology Medicine disc, Chinese Journals Full-text Database, VIP Database, and Wanfang Database were searched using key words in Chinese version "," to obtain the randomized controlled trials about rhGH in the treatment of adults with severe burn from the establishment of each database to December 2016...
September 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28923883/microtubules-associated-rac-regulation-of-endothelial-barrier-a-role-of-asef-in-acute-lung-injury
#10
Pratap Karki, Anna A Birukova
The endothelial barrier function regulated by the cytoskeletal reorganizations has been implicated in the pathogenesis of multiple lung diseases including asthma, sepsis, edema, and acute respiratory distress syndrome. The extensive studies have established that activation of small GTPase Rac is a key mechanism in endothelial barrier protection but the role of microtubules-associated Rac in the endothelial functions remains poorly understood. With the emerging evidences that microtubules disassembly also plays a critical role in actin cytoskeleton remodeling leading to endothelial permeability, the knowledge on microtubules-mediated regulation of endothelial barrier is imperative to better understand the etiology of lung injuries as well as to develop novel therapeutics against these disorders...
September 18, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28922428/diminished-neutrophil-extracellular-trap-net-formation-is-a-novel-innate-immune-deficiency-induced-by-acute-ethanol-exposure-in-polymicrobial-sepsis-which-can-be-rescued-by-cxcl1
#11
Liliang Jin, Sanjay Batra, Samithamby Jeyaseelan
Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens. Animal models and human studies demonstrate that alcohol intoxication is a key risk factor for sepsis-induced mortality. Multiple chemokines, such as CXCL1, CXCL2 and CXCL5 are critical for neutrophil recruitment and proper function of neutrophils. However, it is not quite clear the mechanisms by which acute alcohol suppresses immune responses and whether alcohol-induced immunosuppression can be rescued by chemokines...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28901393/lps%C3%A2-induced-downregulation-of-microrna%C3%A2-204-211-upregulates-and-stabilizes-angiopoietin%C3%A2-1-mrna-in-ea-hy926-endothelial-cells
#12
Yijun Zhang, Caixia Gan, Jiangbo Zhang, Dong Chen
Angiopoietin‑1 (ANG‑1), a ligand of the endothelial cell‑specific TIE2 surface receptor, acts in a complementary and coordinated manner with vascular endothelial growth factor during the process of angiogenesis. ANG‑1 can be used as a clinically informative biomarker of disease severity and outcome in severe sepsis. The epithelium‑specific Ets transcription factor 1 can activate ANG‑1 transcription in the setting of inflammation; however, relatively little is known about the regulation of ANG‑1 by microRNAs (miRs)...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28895695/bronchopulmonary-dysplasia-incidence-and-risk-factors
#13
Pablo H Brener Dik, Yeimy M Niño Gualdron, María F Galletti, Carolina M Cribioli, Gonzalo L Mariani
INTRODUCTION: Bronchopulmonary dysplasia is the most common chronic pulmonary sequela among very low birth weight infants. The objective of this study was to estimate its incidence in our Neonatal Unit over the past 5 years and analyze associated risk factors. POPULATION AND METHODS: An observational and analytical study was conducted in a retrospective cohort, using data obtained from a prospective database of infants born at Hospital Italiano de Buenos Aires with a birth weight of less than 1500 grams between January 2010 and December 2014...
October 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28884304/cell-cycle-arrest-biomarkers-in-urine-to-predict-acute-kidney-injury-in-septic-and-non-septic-critically-ill-patients
#14
M Cuartero, J Ballús, J Sabater, X Pérez, N Nin, J Ordonez-Llanos, A J Betbesé
PURPOSE: To analyse the usefulness of the composite index of the tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as urinary biomarkers for the early prediction of AKI in septic and non-septic patients. METHODS: This is a prospective, observational study including patients admitted to ICU from acute care departments and hospital length of stay <48 h. The main exclusion criteria were pre-existing eGFR <30 mL/min/1...
September 7, 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/28879784/non-chemotherapy-drug-induced-neutropenia-an-update
#15
REVIEW
Emmanuel Andrès, Rachel Mourot-Cottet
To date, non-chemotherapy drug-induced severe neutropenia (neutrophil count of ≤0.5 x 10(9)/L) also called idiosyncratic drug-induced agranulocytosis is little discussed in the literature. In the present paper, we report and discuss the clinical data and management of this rare disorder. Areas covered: To do this, we carried out a review of the literature using PubMed database of the US National Library of Medicine. We also used data from the American Society of Hematology educational books, textbooks of Hematology and Internal medicine, and information gleaned from international meetings...
November 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28872079/-mechanisms-for-the-regulatory-effect-of-prostaglandin-e2-prostaglandin-e-receptor-4-on-high-mobility-group-box-1-protein-in-lipopolysaccharide-induced-sepsis-in-mouse-peritoneal-macrophage
#16
Xiaoliang Wang, Yong Zhang, Yanna Si, Yajie Xu, Hongguang Bao, Xiaoming Bai, Jing Leng
To explore the effect of prostaglandin E2 (PGE2) on the expression of high mobility group box-1 protein (HMGB1) in peritoneal macrophages of septic mice and its possible mechanisms.
 Methods: The mouse peritoneal macrophages were isolated and cultured by conventional methods.The model of inflammation was established by using lipopolysaccharide (LPS) to incubate with mouse peritoneal macrophages. The PGE2, prostaglandin E receptor (EP) 4 agonist, EP4 RNAi, and DN.CREB inhibitory plasmid were used to interfere with the LPS-treated mouse peritoneal macrophage...
August 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28833725/nutritional-intake-and-growth-velocity-in-preterm-extremely-low-birthweight-infants-in-asia-are-we-doing-enough
#17
Shilpee Raturi, Qishi Zheng, Lourdes M Daniel, Luming Shi, Victor S Rajadurai, Pratibha K Agarwal
AIM: To describe nutritional practices among preterm extremely low-birthweight (ELBW) infants and their impact on growth and to compare differences in nutritional intervention and comorbidities between those with limited growth velocity (GV < 25th percentile) and those with GV > 25th percentile. METHODS: A prospective cohort study was conducted to assess total protein and energy intake for week 1, days 14, 21 and 28 of life. Post-natal growth was calculated by measuring GV using an exponential model...
August 18, 2017: Journal of Paediatrics and Child Health
https://www.readbyqxmd.com/read/28746898/circulating-levels-of-the-angiogenesis-mediators-endoglin-hb-egf-bmp-9-and-fgf-2-in-patients-with-severe-sepsis-and-septic-shock
#18
Vanessa Boury Faiotto, Daniel Franci, Rodolfo Monteiro Enz Hubert, Gleice Regina de Souza, Maiara Marx Luz Fiusa, Bidossessi Wilfried Hounkpe, Thiago Martins Santos, Marco Antonio Carvalho-Filho, Erich Vinicius De Paula
PURPOSE: Endothelial barrier dysfunction is a hallmark of sepsis, and is at least partially mediated by pathways that regulate endothelial barrier assembly during angiogenesis. Not surprisingly, increased levels of key angiogenic proteins such as VEGF-A and Angiopoietin-2 have been described in sepsis. The purpose of this study was to investigate if additional pathways that regulate endothelial barrier integrity during angiogenesis could also be involved in the host response of sepsis...
July 17, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28728751/a-phase-ii-evaluation-of-brivanib-in-the-treatment-of-persistent-or-recurrent-carcinoma-of-the-cervix-an-nrg-oncology-gynecologic-oncology-group-study
#19
John K Chan, Wei Deng, Robert V Higgins, Krishnansu S Tewari, Albert J Bonebrake, Michael Hicks, Stephanie Gaillard, Pedro T Ramirez, Weldon Chafe, Bradley J Monk, Carol Aghajanian
BACKGROUND: Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients. METHODS: Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity...
September 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28716993/low-soluble-fms-like-tyrosine-kinase-1-endoglin-and-endothelin-1-levels-in-women-with-confirmed-or-suspected-preeclampsia-using-proton-pump-inhibitors
#20
Langeza Saleh, Raaho Samantar, Ingrid M Garrelds, Anton H van den Meiracker, Willy Visser, A H Jan Danser
Patients with preeclampsia display elevated placenta-derived sFlt-1 (soluble Fms-like tyrosine kinase-1) and endoglin levels and decreased placental growth factor levels. Proton pump inhibitors (PPIs) decrease trophoblast sFlt-1 and endoglin secretion in vitro. PPIs are used during pregnancy to combat reflux disease. Here, we investigated whether PPIs affect sFlt-1 in women with confirmed/suspected preeclampsia, making use of a prospective cohort study involving 430 women. Of these women, 40 took PPIs (6 esomeprazole, 32 omeprazole, and 2 pantoprazole) for 8 to 45 (median 29) days before sFlt-1 measurement...
September 2017: Hypertension
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